Heterodimerization between 5‐HT7 and 5‐HT1A receptors seems to play an important role in the mechanism of depression and antidepressant drug action. It was suggested that the shift of the ratio between 5‐HT1A/5‐HT7 hetero‐ and 5‐HT1A/5‐HT1A homodimers in presynaptic neurons toward 5‐HT1A/5‐HT1A homodimers is one of the reasons of depression. Consequently, the artificial elevation of 5‐HT7 receptor number in presynaptic terminals might restore physiological homo‐/heterodimer ratio resulting in antidepressive effect. Here we showed that adeno‐associated virus (AAV)‐based 5‐HT7 receptor overexpression in the midbrain raphe nuclei area produced antidepressive effect in male mice of both C57Bl/6J and genetically predisposed to depressive‐like behavior ASC (antidepressant sensitive cataleptics) strains. These changes were accompanied by the elevation of 5‐HT7 receptor mRNA level in the frontal cortex of C57Bl/6J and its reduction in the hippocampus of ASC mice. The presence of engineered 5‐HT7 receptor in the midbrain of both mouse strains was further demonstrated. Importantly that 5‐HT7 receptor overexpression resulted in the reduction of 5‐HT1A receptor level in the membrane protein fraction from the midbrain samples of C57Bl/6J, but not ASC, mice. 5‐HT7 receptor overexpression caused an increase of 5‐HIAA/5‐HT ratio in the midbrain and the frontal cortex of C57Bl/6J and in all investigated brain structures of ASC mice. Thus, 5‐HT7 receptor overexpression in the raphe nuclei area affects brain 5‐HT system and causes antidepressive effect both in C57Bl/6J and in “depressive” ASC male mice. Obtained results indicate the involvement of 5‐HT7 receptor in the mechanisms underlying depressive behavior.
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